KEAP1-mutant atypical meningioma: illustrative case.

BACKGROUND: While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported. OBSERVATIONS: The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS. LESSONS: To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.

Protocol for human brain organoid transplantation into a rat visual cortex to model neural repair.

Human stem-cell-derived organoids represent a promising substrate for transplantation-based neural repair. Here, we describe a protocol for transplanting forebrain organoids into an injured adult rat visual cortex. This protocol includes surgical details for craniectomy, aspiration injury, organoid transplantation, and cranioplasty. This platform represents a valuable tool for investigating the efficacy of organoids as structured grafts for neural repair. For complete details on the use and execution of this protocol, please refer to Jgamadze et al.1.

Cell Replacement Therapy for Brain Repair: Recent Progress and Remaining Challenges for Treating Parkinson's Disease and Cortical Injury.

Neural transplantation represents a promising approach to repairing damaged brain circuitry. Cellular grafts have been shown to promote functional recovery through "bystander effects" and other indirect mechanisms. However, extensive brain lesions may require direct neuronal replacement to achieve meaningful restoration of function. While fetal cortical grafts have been shown to integrate with the host brain and appear to develop appropriate functional attributes, the significant ethical concerns and limited availability of this tissue severely hamper clinical translation. Induced pluripotent stem cell-derived cells and tissues represent a more readily scalable alternative. Significant progress has recently been made in developing protocols for generating a wide range of neural cell types in vitro. Here, we discuss recent progress in neural transplantation approaches for two conditions with distinct design needs: Parkinson's disease and cortical injury. We discuss the current status and future application of injections of dopaminergic cells for the treatment of Parkinson's disease as well as the use of structured grafts such as brain organoids for cortical repair.

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.